Pembrolizumab monotherapy versus chemotherapy in platinum-pretreated, recurrent or metastatic nasopharyngeal cancer (KEYNOTE-122): an open-label, randomized, phase III trial.

BACKGROUND: Pembrolizumab previously demonstrated robust antitumor activity and manageable safety in a phase Ib study of patients with heavily pretreated, programmed death ligand 1 (PD-L1)-positive, recurrent or metastatic nasopharyngeal carcinoma (NPC). The phase III KEYNOTE-122 study was conducted to further evaluate pembrolizumab versus chemotherapy in patients with platinum-pretreated, recurrent and/or metastatic NPC. Final analysis results are presented. PATIENTS AND METHODS: KEYNOTE-122 was an open-label, randomized study conducted at 29 sites, globally. Participants with platinum-pretreated recurrent and/or metastatic NPC were randomly assigned (1 : 1) to pembrolizumab or chemotherapy with capecitabine, gemcitabine, or docetaxel. Randomization was stratified by liver metastasis (present versus absent). The primary endpoint was overall survival (OS), analyzed in the intention-to-treat population using the stratified log-rank test (superiority threshold, one-sided P = 0.0187). Safety was assessed in the as-treated population. RESULTS: Between 5 May 2016 and 28 May 2018, 233 participants were randomly assigned to treatment (pembrolizumab, n = 117; chemotherapy, n = 116); Most participants (86.7%) received study treatment in the second-line or later setting. Median time from randomization to data cut-off (30 November 2020) was 45.1 months (interquartile range, 39.0-48.8 months). Median OS was 17.2 months [95% confidence interval (CI) 11.7-22.9 months] with pembrolizumab and 15.3 months (95% CI 10.9-18.1 months) with chemotherapy [hazard ratio, 0.90 (95% CI 0.67-1.19; P = 0.2262)]. Grade 3-5 treatment-related adverse events occurred in 12 of 116 participants (10.3%) with pembrolizumab and 49 of 112 participants (43.8%) with chemotherapy. Three treatment-related deaths occurred: 1 participant (0.9%) with pembrolizumab (pneumonitis) and 2 (1.8%) with chemotherapy (pneumonia, intracranial hemorrhage). CONCLUSION: Pembrolizumab did not significantly improve OS compared with chemotherapy in participants with platinum-pretreated recurrent and/or metastatic NPC but did have manageable safety and a lower incidence of treatment-related adverse events.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with intermediate and advanced/relapsed hepatocellular carcinoma: a TOS-ESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and SSO.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of hepatocellular carcinoma (HCC) was published in 2018, and covered the diagnosis, management, treatment and follow-up of early, intermediate and advanced disease. At the ESMO Asia Meeting in November 2018 it was decided by both the ESMO and the Taiwan Oncology Society (TOS) to convene a special guidelines meeting immediately after the Taiwan Joint Cancer Conference (TJCC) in May 2019 in Taipei. The aim was to adapt the ESMO 2018 guidelines to take into account both the ethnic and the geographic differences in practice associated with the treatment of HCC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with intermediate and advanced/relapsed HCC representing the oncology societies of Taiwan (TOS), China (CSCO), India (ISMPO) Japan (JSMO), Korea (KSMO), Malaysia (MOS) and Singapore (SSO). The voting was based on scientific evidence, and was independent of the current treatment practices, the drug availability and reimbursement situations in the individual participating Asian countries.

In vivo dosimetry using MOSkin detector during Cobalt-60 high-dose-rate (HDR) brachytherapy of skin cancer.

The MOSkin, a metal-oxide semiconductor field-effect transistor based detector, is suitable for evaluating skin dose due to its water equivalent depth (WED) of 0.07 mm. This study evaluates doses received by target area and unavoidable normal skin during a the case of skin brachytherapy. The MOSkin was evaluated for its feasibility as detector of choice for in vivo dosimetry during skin brachytherapy. A high-dose rate Cobalt-60 brachytherapy source was administered to the tumour located at the medial aspect of the right arm, complicated with huge lymphedema thus limiting the arm motion. The source was positioned in the middle of patients' right arm with supine, hands down position. A 5 mm lead and 5 mm bolus were sandwiched between the medial aspect of the arm and lateral chest to reduce skin dose to the chest. Two calibrated MOSkin detectors were placed on the target and normal skin area for five treatment sessions for in vivo dose monitoring. The mean dose to the target area ranged between 19.9 and 21.1 Gy and was higher in comparison with the calculated dose due to contribution of backscattered dose from lead. The mean measured dose at normal skin chest area was 1.6 Gy (1.3-1.9 Gy), less than 2 Gy per fraction. Total dose in EQD2 received by chest skin was much lower than the recommended skin tolerance. The MOSkin detector presents a reliable real-time dose measurement. This study has confirmed the applicability of the MOSkin detector in monitoring skin dose during brachytherapy treatment due to its small sensitive volume and WED 0.07 mm.

In vivo skin dose measurement using MOSkin detectors in tangential breast radiotherapy.

The purpose of this study is to measure patient skin dose in tangential breast radiotherapy. Treatment planning dose calculation algorithm such as Pencil Beam Convolution (PBC) and in vivo dosimetry techniques such as radiochromic film can be used to accurately monitor radiation doses at tissue depths, but they are inaccurate for skin dose measurement. A MOSFET-based (MOSkin) detector was used to measure skin dose in this study. Tangential breast radiotherapies ("bolus" and "no bolus") were simulated on an anthropomorphic phantom and the skin doses were measured. Skin doses were also measured in 13 patients undergoing each of the techniques. In the patient study, the EBT2 measurements and PBC calculation tended to over-estimate the skin dose compared with the MOSkin detector (p<0.05) in the "no bolus radiotherapy". No significant differences were observed in the "bolus radiotherapy" (p>0.05). The results from patients were similar to that of the phantom study. This shows that the EBT2 measurement and PBC calculation, while able to predict accurate doses at tissue depths, are inaccurate in predicting doses at build-up regions. The clinical application of the MOSkin detectors showed that the average total skin doses received by patients were 1662±129cGy (medial) and 1893±199cGy (lateral) during "no bolus radiotherapy". The average total skin doses were 4030±72cGy (medial) and 4004±91cGy (lateral) for "bolus radiotherapy". In some cases, patient skin doses were shown to exceed the dose toxicity level for skin erythema. Hence, a suitable device for in vivo dosimetry is necessary to accurately determine skin dose.

Breast Cancer Outcomes as Defined by the Estrogen Receptor, Progesterone Receptor, and Human Growth Factor Receptor-2 in a Multi-ethnic Asian Country.

INTRODUCTION: Breast cancer can be divided into four subtypes based on the expressions of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor-2 (HER2). Each subtype has different clinicopathological features and outcomes. OBJECTIVE: To compare the clinicopathological features and survival of ER and/or PR positive HER2 negative (ER+PR+HER2-, ER+PR-HER2- or ER-PR+HER2-), ER and/or PR positive HER2 positive (ER+PR+HER2+, ER+PR-HER2+ or ER-PR+HER2+), ER negative PR negative HER2 positive (ER-PR-HER2+), and ER negative PR negative HER2 negative (ER-PR-HER2-) subtypes. METHODS: 1957 patients with Stage 1-3 breast carcinoma diagnosed between Jan 2005 and Dec 2011 were categorized into the four subtypes. The clinicopathological features between the subtypes were compared using χ (2) test. Kaplan-Meier analysis was performed to estimate 5-year overall survival. Multivariate Cox regression was used to determine the association between subtypes and mortality adjusted for age, ethnicity, stage, pathological features, and treatment. RESULTS: ER-PR-HER2+ and ER-PR-HER2- subtypes were associated with younger age, larger tumors, and higher grade. There was no difference in the 5-year survival of the ER-PR-HER2+ and ER-PR-HER2- subtypes (75.1 and 74.4 %, respectively) and survival was poorer than in the ER and/or PR positive HER2 negative and ER and/or PR positive HER2 positive subtypes (87.1 and 83.1 %, respectively). Only 9.5 % of women with HER2 positive breast cancer had access to trastuzumab. CONCLUSION: In a low resource setting with limited access to trastuzumab, there is no difference in survival between the ER-PR-HER2+ and ER-PR-HER2- subtypes of breast cancer.

Prevalence and characteristics associated with default of treatment and follow-up in patients with cancer.

Defaulting is an important issue across all medical specialties, but much more so in cancer as delayed or incomplete treatment has been shown to result in worse clinical outcomes such as treatment resistance, disease progression as well as lower survival. Our objective was to identify psychosocial variables and characteristics associated with default among cancer patients. A total of 467 consecutive adult cancer patients attending the oncology clinic at a single academic medical centre completed the Hospital Anxiety and Depression Scale and reported their preference for psychological support at baseline, 4-6 weeks and 12-18 months follow-up. Default was defined as refusal, delay or discontinuation of treatment or visit, despite the ability to do so. A total of 159 of 467 (34.0%) cancer patients were defaulters. Of these 159 defaulters, 89 (56.0%) desired psychological support, compared to only 13 (4.2%) of 308 non-defaulters. Using a logistic regression, patients who were defaulters had 52 times higher odds (P = 0.001; 95% confidence interval 20.61-134.47) of desiring psychological support than non-defaulters after adjusting for covariates. These findings suggest that defaulters should be offered psychological support which may increase cancer treatment acceptance rates and improve survival.

Comparison of planned and measured rectal dose in-vivo during high dose rate Cobalt-60 brachytherapy of cervical cancer.

Cobalt-60 (Co-60) is a relatively new source for the application of high-dose rate (HDR) brachytherapy. Radiation dose to the rectum is often a limiting factor in achieving the full prescribed dose to the target during brachytherapy of cervical cancer. The aim of this study was to measure radiation doses to the rectum in-vivo during HDR Co-60 brachytherapy. A total of eleven HDR brachytherapy treatments of cervical cancer were recruited in this study. A series of diodes incorporated in a rectal probe was inserted into the patient's rectum during each brachytherapy procedure. Real-time measured rectal doses were compared to calculated doses by the treatment planning system (TPS). The differences between calculated and measured dose ranged from 8.5% to 41.2%. This corresponds to absolute dose differences ranging from 0.3 Gy to 1.5 Gy. A linear relationship was observed between calculated and measured doses with linear regression R(2) value of 0.88, indicating close association between the measured and calculated doses. In general, absorbed doses for the rectum as calculated by TPS were observed to be higher than the doses measured using the diode probe. In-vivo dosimetry is an important quality assurance method for HDR brachytherapy of cervical cancer. It provides information that can contribute to the reduction of errors and discrepancies in dose delivery. Our study has shown that in-vivo dosimetry is feasible and can be performed to estimate the dose to the rectum during HDR brachytherapy using Co-60.

Invasive lobular carcinoma of the breast diagnosed from an ovarian tumour.

Invasive lobular carcinoma of breast is well known to be able to metastasise to unusual places, including the gastrointestinal and gynaecological tracts. However, it is very unusual for breast cancer to present in an ovarian Brenner tumour. This case highlights the diagnostic difficulties of patients presenting with unilateral ovarian masses, and the merits of thorough histological assessment of the entire pathological specimen despite the presence of one obvious pathological diagnosis.